Effects of fine carbonaceous particles containing high and low unpaired electron spin densities on lungs of female mice.
The negative impacts on human health that accompany inhalation of atmospheric particles are documented in numerous epidemiologic studies, but the effect of specific chemical properties of the particles is generally unknown. We developed and employed technology for generating inhalable aerosols of carbonaceous air pollution particles that have specific physical and chemical properties. We find that inhaling particles with greater unpaired electron spin (free radical) densities stimulates greater lung inflammatory and oxidative stress responses. Cultured alveolar macrophages take up more particles of greater free radical content, develop mitochondrial abnormalities, and release more leukotriene B(4) (LTB(4)) than alveolar macrophages exposed to lesser free-radical-containing particles in vitro. Mice exposed to high free radical particles in vivo also develop mitochondrial abnormalities in alveolar macrophages and increased oxidative stress, which is reflected by increases in lung nitrotyrosine staining and lung lavage nitrogen oxide levels compared with those of lesser free radical density. These results provide insight for the unexplained geographic differences and have implications for fossil fuel combustion conditions and the impact of fine particles on health and disease.
Repine
John E
JE
Webb-Waring Institute for Cancer, Aging, and Antioxidant Research, University of Colorado Denver Health Sciences Center, Denver, CO 80262, USA. john.repine@uchsc.edu
Reiss
Oscar K
OK
Elkins
Nancy
N
Chughtai
Abdul R
AR
Smith
Dwight M
DM
D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000032:analysis / Q000378:metabolism; D019570:Inhalation Exposure; D007975:Leukotriene B4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D053260:Soot / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000336:Aerosols; D005609:Free Radicals; D052638:Particulate Matter; D053260:Soot; D007975:Leukotriene B4; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine